: Numerous studies have shown that chronic exposure to various drugs of abuse results in the accumulation of the transcription factor delta FosB (a shorter splice variant of FosB) in specific brain areas including those involved in reward pathways. As FosB, delta FosB can dimerize with Jun proteins to form an activator protein-1 complex (AP-1) that can regulate the expression of many genes. The induction of delta FosB is associated with a shift on its apparent molecular weight, from 33 kDa (delta FosB33) to 37 kDa (delta FosB37), and a dramatic increase in its half-life (from hours to weeks). Moreover, delta FosB induction is not quickly repressed as is that of FosB and other transcription factors. Due to its long half-life and unrepressed induction, delta FosB37 persists in brain long after the last drug exposure. Delta FosB37 has also been shown to elicit behavioral changes in several animal models of drug addiction. Based on the above, it has been hypothesized that delta FosB37 constitutes a form of molecular plasticity involved in drug-associated neuronal adaptations. This hypothesis however, cannot be fully tested until the biochemical and functional profiles of this molecule are understood. Thus, the specific alms of this proposal are: I. Obtain large quantities of delta FosB to perform biochemical analyses II. Determine the nature of the modifications involved in the transition from delta FosB33 to delta FosB37 Ill. Study the consequences of these modifications on delta FosB?s biochemical, and functional profiles The achievement of these aims will shed light not only on delta FosB?s putative role as a mediator of long-term neuronal plasticity, but also on its potential as a therapeutic target for the treatment of drug addiction.